Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To characterize directly the ability of cholecystokinin (CCK) to interact with receptors on the sphincter of Oddi (SO), we measured binding of 125I-labeled Bolton-Hunter-labeled COOH-terminal octapeptide of cholecystokinin (125I-BH-CCK-8) to tissue sections from the guinea pig SO. Autoradiography localized binding of 125I-BH-CCK-8 over the SO smooth muscle layer. Binding was saturable, specific, dependent on time, pH, and temperature, and was reversible. Binding of 125I-BH-CCK-8 was inhibited by various CCK receptor agonists with the following potencies: CCK-8 much greater than des(SO3)CCK-8 much greater than gastrin-17-I and by various CCK receptor antagonists with the following potencies: L-364,718 greater than proglumide analogue 10 much greater than carbobenzoxy-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-NH2 greater than N2,O2' dibutyryl guanosine 3',5'-cyclic monophosphate. The potencies of agonists in stimulating and of antagonists in inhibiting CCK-8-stimulated SO contractions correlated closely with their abilities to inhibit binding of 125I-BH-CCK-8. Analysis of binding of 125I-BH-CCK-8 to SO tissue sections revealed two classes of CCK binding sites: a high-affinity site [dissociation constant (Kd) 0.2 nM] and a low-affinity site (Kd 70 nM). Atropine or tetrodotoxin (TTX) caused a similar rightward shift of the CCK-8 dose-response curve for stimulation of SO contraction. Comparison of receptor occupation to CCK-8-induced contraction suggested that CCK-8 occupation of the high-affinity binding site correlated with contraction in the absence of atropine and the low-affinity CCK binding with contraction in the presence of atropine or TTX.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of cholecystokinin receptors on the sphincter of Oddi. 224 Feb 27

The effect of gastric distension on plasma cholecystokinin (CCK), pancreatic polypeptide (PP) and gastrin concentrations was investigated in healthy volunteers. Fundic and antral distension was achieved by balloons attached to a gastric tube and inflated with 300 and 600 ml and 100 and 200 ml of air for fundic and antral distension, respectively. Gastric juice was continuously aspirated. Fundic distension was additionally studied during a concomitant intravenous infusion of atropine (5 micrograms/kg/h) or a bolus injection of propranolol (2 mg). Fundic distension with 300 ml caused a significant increase in PP release (+17% above basal). Distension with 600 ml significantly stimulated CCK (+81%), gastrin (+31%) and PP output (+74%) over 30 min. Atropine completely blocked PP release and almost abolished CCK release, whereas gastrin output was enhanced. Propranolol did not prevent CCK release induced by fundic distension, whereas gastrin and PP responses were diminished. Antral distension did not cause any significant changes in hormone response. In conclusion, we demonstrated a gastric phase of CCK release which is atropine sensitive, but not influenced by propranolol.
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PMID:Cholecystokinin release by gastric distension--an atropine-sensitive mechanism. 228 97

The effects of loxiglumide, a potent cholecystokinin (CCK)-receptor antagonist, and atropine, a muscarinic receptor blocker, on exocrine pancreatic secretion stimulated by hormones (secretin plus CCK) and a Lundh test meal were studied in healthy young volunteers. Loxiglumide infused intravenously in gradually increasing doses (2-16 mumol/kg-h) caused a dose-dependent inhibition of pancreatic enzyme secretion induced by intravenous infusion of a constant dose of secretin (82 pmol/kg-h) plus CCK-8 (85 pmol/kg-h) but had relatively smaller influence on duodenal volume flow and bicarbonate output. Atropine (20 nmol/kg) also caused a significant reduction in pancreatic enzyme secretion but failed to affect the volume flow or bicarbonate secretion induced by secretin plus CCK, possibly owing to the high doses of secretin and CCK used in these tests. Both loxiglumide and atropine inhibited the pancreatic enzyme response to a Lundh meal, but atropine was more effective in the early phase and loxiglumide in the late phase of the postprandial secretion. Neither loxiglumide nor atropine affected the plasma gastrin and CCK levels, but both antagonists reduced plasma pancreatic polypeptide responses to the Lundh meal. We conclude that 1) loxiglumide results in a relatively stronger suppression of the pancreatic enzyme than aqueous-alkaline secretion induced by secretin plus CCK, whereas atropine inhibits only enzyme secretion; and 2) both loxiglumide and atropine suppress the pancreatic enzyme responses to the meal stimulation without affecting the postprandial plasma gastrin and CCK responses.
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PMID:Comparison of loxiglumide, a cholecystokinin receptor antagonist, and atropine on hormonal and meal-stimulated pancreatic secretion in man. 239 88

After a meal, the absorption of water and electrolytes from the jejunal lumen increases. This meal-induced jejunal absorption occurs in jejunal segments out of normal gastrointestinal continuity. The experimental model used 25-cm proximal jejunal Thiry-Vella loops in awake dogs (n = 72 observations) to evaluate the mechanisms involved in meal-induced jejunal absorption, seeking to define the source or sources of the proabsorptive signal. Specifically, we evaluated the jejunal absorptive response to a standard meal, a standard meal plus cholinergic blockage using atropine, a sham-fed meal, a gavage-fed meal, and gastric distension with balloon and gavage water. Both the standard meal and the gavage-fed meal induced a prompt, sustained, and significant (P less than 0.0001) increase in the absorption of H2O, Na+, and Cl-. Atropine significantly reduced the magnitude of the postmeal absorptive response (P less than 0.05) compared with the standard meal alone. The sham-fed meal, gastric balloon distension, and gavage water did not alter jejunal absorption. Vagal nerve integrity after cervical esophageal manipulation was verified by gastric acid output and gastrin response to stimuli. These data support a role for cholinergic modulation of meal-stimulated jejunal absorption via a cephalic-phase-independent and gastric-distension-independent mechanism.
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PMID:Meal-stimulated absorption of water and electrolytes in canine jejunum. 239 84

Although cholecystokinin (CCK) has been reported to stimulate pepsinogen secretion, this action has been poorly characterized. To assess the ability of CCK to regulate mammalian pepsinogen secretion, guinea pig fundic mucosa was incubated in Ussing chambers with CCK-8, carbamylcholine, and pentagastrin, and with cholinergic and CCK antagonists. CCK-8 stimulated pepsinogen secretion at 10(-10) M, with an ED50 of 10(-9) M and maximally (26-fold over basal) at 10(-8) M. Carbachol stimulated pepsinogen and acid secretion with an ED50 of 3 x 10(-7) M and maximally at 10(-6) M. Pentagastrin (10(-9) M-10(-6) M) did not affect acid or pepsinogen secretion, whereas gastrin-I (10(-6) M) stimulated acid secretion slightly but did not alter pepsinogen secretion. L364, 718 (10(-5) M), a specific CCK peripheral receptor antagonist, abolished all pepsigogic effects of 3 x 10(-9) M CCK-8 without altering basal acid or pepsinogen secretion or mucosal electric characteristics. L364,718-treated tissues unresponsive to CCK-8 nevertheless secreted pepsinogen and acid in response to 3 x 10(-7) M carbachol identically to control carbachol-treated preparations. Atropine (10(-5) M) blocked the response to 3 x 10(-7) M carbachol without inhibiting 10(-9) M CCK stimulation. These results support a specific receptor-mediated role for cholecystokinin in the physiologic regulation of guinea pig pepsinogen secretion.
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PMID:Effects of cholecystokinin and cholinergic receptor blockade on guinea pig pepsinogen secretion. 240 88

The purpose of this study was to determine the role of gastrin and cholecystokinin in the cephalic phase of gastrin release and gastric and pancreatic secretion in conscious dogs. Sham feeding in intact dogs increased gastric acid output to about 65% of histamine maximum and pancreatic protein to 23% of caerulein maximum. Significant increases in plasma gastrin and pancreatic polypeptide but not cholecystokinin occurred. Similar effects were obtained using insulin hypoglycemia or 2-deoxy-D-glucose glucocytopemia. Atropine eliminated gastric acid response to sham feeding, insulin, or 2-deoxy-D-glucose, significantly reduced the pancreatic protein response by about 60%, and abolished plasma pancreatic polypeptide but not plasma gastrin. Blocking of cholecystokinin receptors by L-364,715 did not affect gastric or pancreatic secretory responses to sham feeding, insulin, or 2-deoxy-D-glucose and failed to influence the accompanying increments in plasma gastrin and pancreatic polypeptide. In antral-mucosectomized dogs, sham feeding-induced acid output reached only 17% of histamine maximum but the increase in pancreatic protein output was similar to that in intact dogs. In these animals, background stimulation with G17I (62 pmol/kg per h) potentiated the gastric acid response to sham feeding but had little effect on pancreatic protein output. This study provides evidence that unlike gastric acid, the pancreatic protein response to physiological or pharmacological cephalic stimulation does not depend on vagally released gastrin but probably on direct vagal stimulation of the pancreas.
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PMID:Effects of an antral mucosectomy, L-364,718 and atropine on cephalic phase of gastric and pancreatic secretion in dogs. 240 31

The effects on pancreatic responses of highly potent cyclic hexapeptide (cyclo (N-Me-Ala-Phe-D-Trp-Lys-Thr-Phe)) (Veber analog) and octapeptide analogs of somatostatin such as D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol (SMS 201-995), D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121), and D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) have been compared with somatostatin tetradecapeptide (SS-14) and atropine. The parameters evaluated were pancreatic responses to secretin and meat feeding in conscious dogs with chronic pancreatic fistula and amylase release from the dispersed pancreatic acini. The analogs were administered intravenously or intraduodenally. The cyclic hexapeptide and octapeptide analogs, given iv in graded doses against a constant background stimulation with secretin, produced similar and dose-dependent inhibition of pancreatic HCO3- and protein secretion. Analogs RC-121, RC-160, and the Veber analog were about two to four times more active than SS-14 in suppressing HCO3- secretion and equipotent in reducing protein secretion, but SMS 201-995 was only about half as potent as somatostatin in inhibiting HCO3-. RC-160 was effective in inhibiting secretin-induced protein secretion at lower doses than other analogs. In tests with feeding, SMS 201-995, the Veber analog, RC-121, and RC-160 were more potent inhibitors of exocrine pancreatic secretion of HCO3- and protein and exhibited more prolonged inhibitory effects than SS-14. The Veber analog, RC-121, and RC-160 were also more effective after intraduodenal administration. Atropine also caused significant inhibition of both HCO3- and protein responses to secretin and meal feeding. All four analogs decreased the postprandial insulin and pancreatic polypeptide release to a similar degree as SS-14. Neither SS-14 nor the analogs tested significantly affected basal or caerulein-, gastrin-, secretin-, or bethanechol-stimulated amylase release from the dispersed canine pancreatic acini. Atropine reduced amylase release induced by bethanechol, but not that stimulated by caerulein, gastrin, or secretin. This indicated that the analogs, as somatostatin, are ineffective as secretory inhibitors in vitro. We conclude that cyclic hexapeptide and octapeptide analogs are more potent and longer acting inhibitors of pancreatic secretion than somatostatin-14 in vivo.
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PMID:Comparison of somatostatin and its highly potent hexa- and octapeptide analogs on exocrine and endocrine pancreatic secretion. 244 2

In monogastric animals, suckling influences the secretion of gastrointestinal hormones during lactation. The aim of the present study was to investigate whether similar effects are induced by milking in cows. Experiments were performed on four cows in midlactation. Blood samples were drawn from a chronic jugular vein catheter and gastrin, and somatostatin were determined by radioimmunoassay. Milking and feeding increased plasma gastrin. Somatostatin increased at morning milking and at feeding, but it decreased at evening milking. Atropine injected subcutaneously 30 min before milking increased resting concentrations of gastrin but decreased resting concentrations of somatostatin. Feeding-induced release of gastrin remained but the milking-induced release disappeared. The milking- and feeding-induced effect on somatostatin became more marked. We suggest that milking influences gastrin and somatostatin via activation of the vagal nerves. The gastrin release caused by milking may be mediated via a cholinergic mechanism, whereas the atropine resistant effect on gastrin caused by feeding and on somatostatin caused by both milking and feeding suggest that a noncholinergic, perhaps peptidergic, transmitter may be involved.
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PMID:Milking and feeding-induced release of the gastrointestinal hormones gastrin and somatostatin in dairy cows. 257 1

To investigate the effects of acute hypercalcemia on exocrine pancreatic secretion, anesthetized cats were given calcium intravenously. Increasing hypercalcemia (3.7-6.3 mmol/L) evoked a dose-dependent increase in enzyme output that was 12 times greater than in normocalcemic controls (p less than 0.001) and was 60% of subsequent maximal stimulation with intravenous cholecystokinin (CCK). The effect of hypercalcemia on enzyme secretion was abolished when CCK was administered 60 min before calcium and at a dose to cause maximal enzyme output. Atropine did not prevent the calcium-induced increase in enzyme secretion. Pancreatic fluid and bicarbonate outputs were not influenced by hypercalcemia during intravenous administration of small amounts of secretin, but were increased by addition of CCK to the secretin infusion. Hypercalcemia did not induce macroscopic or light-microscopic changes in pancreatic morphology. Plasma levels of both CCK and gastrin were increased (p less than 0.01) during hypercalcemia, with and without precalcium administration of CCK; atropine significantly inhibited (p less than 0.05), but did not abolish the calcium-induced releases of both peptides. These data suggest that in the anesthetized cat, acute hypercalcemia induced by intravenous calcium infusion stimulates pancreatic secretion of enzymes, but not fluid and bicarbonate. Acute hypercalcemia also causes release of CCK and, as shown previously, gastrin. The findings suggest that the stimulatory effect of hypercalcemia on pancreatic enzyme secretion is not dependent on intact cholinergic pathways and is probably not exclusively mediated by release of CCK or gastrin.
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PMID:Effects of acute hypercalcemia on exocrine pancreatic secretion in the cat. 257 66

The purpose of these studies was to measure circulating gastrin and somatostatin concentrations during sham feeding in humans and to evaluate the effect of two doses of intravenous atropine on circulating concentrations of these peptides. Gastric acid and bicarbonate secretion and pulse rate were also measured. Sham feeding increased plasma gastrin concentrations by approximately 15 pg/ml but had no effect on plasma somatostatin-like immunoreactivity (SLI). A small dose of atropine (5 micrograms/kg) augmented plasma gastrin concentrations during sham feeding significantly (P less than 0.01), but did not affect plasma SLI. Atropine also significantly inhibited gastric acid secretion and gastric bicarbonate secretion (by 62% and 52%, respectively), but pulse rate was not affected. A larger dose of atropine (15 micrograms/kg intravenously) suppressed plasma gastrin concentrations significantly compared to the smaller 5 micrograms/kg atropine dose (P less than 0.02), so that plasma gastrin concentrations when 15 micrograms/kg atropine was given were not significantly different from those during the control study. 15 micrograms/kg atropine reduced gastric acid and bicarbonate secretion by 81% and 66%, respectively, and also increased pulse rate by 15 min-1. These studies indicate that small doses of atropine enhance vagally mediated gastrin release in humans, probably by blocking a cholinergic inhibitory pathway for gastrin release. Although the nature of this cholinergic inhibitory mechanism is unclear, we found no evidence to incriminate somatostatin. Our finding that the larger dose of atropine reduced serum gastrin concentrations compared with the smaller dose suggests that certain vagal-cholinergic pathways may facilitate gastrin release.
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PMID:Effect of atropine on plasma gastrin and somatostatin concentrations during sham feeding in man. 286 96


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